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Essential Role of CED-4 Oligomerization in CED-3 Activation and Apoptosis

Yang, Xiaolu and Chang, Howard Y. and Baltimore, David (1998) Essential Role of CED-4 Oligomerization in CED-3 Activation and Apoptosis. Science, 281 (5381). pp. 1355-1357. ISSN 0036-8075. http://resolver.caltech.edu/CaltechAUTHORS:20141124-102100187

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Abstract

Control of the activation of apoptosis is important both in development and in protection against cancer. In the classic genetic model Caenorhabditis elegans, the pro-apoptotic protein CED-4 activates the CED-3 caspase and is inhibited by the Bcl-2–like protein CED-9. Both processes are mediated by protein-protein interaction. Facilitating the proximity of CED-3 zymogen molecules was found to induce caspase activation and cell death. CED-4 protein oligomerized in cells and in vitro. This oligomerization induced CED-3 proximity and competed with CED-4:CED-9 interaction. Mutations that abolished CED-4 oligomerization inactivated its ability to activate CED-3. Thus, the mechanism of control is that CED-3 in CED-3:CED-4 complexes is activated by CED-4 oligomerization, which is inhibited by binding of CED-9 to CED-4.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1126/science.281.5381.1355DOIArticle
http://www.sciencemag.org/content/281/5381/1355PublisherArticle
ORCID:
AuthorORCID
Baltimore, David0000-0001-8723-8190
Additional Information:© 1998 American Association for the Advancement of Science. Received 3 June 1998; accepted 13 July 1998. We thank F. Chen and H. R. Horvitz for reagents and discussions, P. Svec and A. Darbinian for technical support, and V. M. Dixit, M. Gilman, S. L. Schreiber, and X. Wang for reagents. Supported by the Leukemia Society of America (to X.Y.), the Medical Scientist Training Program (to H.Y.C.), and NIH grant CA51462.
Funders:
Funding AgencyGrant Number
Leukemia Society of AmericaUNSPECIFIED
NIH CA51462
Record Number:CaltechAUTHORS:20141124-102100187
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20141124-102100187
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:52093
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:24 Nov 2014 21:27
Last Modified:06 Nov 2017 23:20

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